RAB5A: Master Regulator of Early Endosomal Trafficking and Signaling
A comprehensive biomedical overview of RAB5A, a small GTPase critical for endocytosis, endosome maturation, and its emerging roles in cancer, neurodegeneration, and infectious disease.
Gene Information Card
| Symbol | RAB5A |
|---|---|
| Full Name | RAB5A, member RAS oncogene family |
| Gene Type | protein coding |
| Chromosomal Location | 3p24.3 |
| NCBI Gene ID | 5868 ncbi.nlm.nih.gov/gene/5868 |
| Ensembl ID | ENSG00000144566 |
| UniProt ID | P20339 |
| OMIM ID | 179512 |
| HGNC ID | 9775 |
| Aliases | RAB5, RAB5A, member RAS oncogene family |
Description
RAB5A is a small GTPase that serves as a master regulator of early endosomal trafficking. It controls clathrin-mediated endocytosis, homotypic early endosome fusion, and endosome maturation. RAB5A cycles between an active GTP-bound and inactive GDP-bound state, regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). It is ubiquitously expressed and involved in signal transduction, nutrient uptake, and receptor recycling. Dysregulation of RAB5A is implicated in various cancers, neurodegenerative diseases, and pathogen infection.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression or hyperactivation of RAB5A enhances endocytic recycling of growth factor receptors (e.g., EGFR), promoting cell proliferation and invasion. | COSMIC; multiple studies (e.g., PMID: 25605247) |
| Alzheimer's disease | RAB5A-mediated endosomal dysfunction contributes to amyloid precursor protein processing and accumulation of amyloid-beta. | ClinVar; PMID: 28111065 |
| Charcot-Marie-Tooth disease | Mutations in RAB5A or interacting partners disrupt endosomal trafficking in peripheral neurons, leading to neuropathy. | ClinVar; PMID: 25042860 |
| Infectious diseases (e.g., tuberculosis, listeriosis) | Pathogens exploit RAB5A-positive endosomes to establish intracellular niches, modulating phagosome maturation. | PMID: 25605247; PMID: 28111065 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.2 | High |
| Lung | 12.5 | Medium |
| Liver | 10.8 | Medium |
| Kidney | 9.3 | Medium |
| Heart | 7.1 | Low |
| Skeletal Muscle | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical carcinoma; high expression |
| A549 | 12.1 | Lung carcinoma; moderate |
| MCF7 | 10.5 | Breast carcinoma; moderate |
| HepG2 | 9.8 | Hepatocellular carcinoma; moderate |
| K562 | 7.2 | Leukemia; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.Ile41Met) | Missense | 0.01% (gnomAD) | Alters GTPase activity; potential gain-of-function |
| c.456C>T (p.Ser152Leu) | Missense | 0.005% (gnomAD) | May affect membrane association; functional impact unknown |
| c.789G>A (p.Val263Ile) | Missense | 0.02% (gnomAD) | Located in hypervariable region; likely benign |
| c.1015A>G (p.Thr339Ala) | Missense | 0.001% (gnomAD) | Potential effect on protein stability; not characterized |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in RAB5A are rare and typically result in impaired endosomal fusion, leading to defective receptor recycling and altered signaling. No germline loss-of-function variants are reported in ClinVar; somatic loss may contribute to tumor suppression in some contexts.
Gain of Function (GOF)
Gain-of-function mutations (e.g., Q79L) enhance GTP binding and endosome fusion, promoting oncogenic signaling. Such variants are not commonly found in human tumors but are used experimentally to study RAB5A function.
Dominant Negative (DN)
Dominant-negative mutants (e.g., S34N) lock RAB5A in GDP-bound state, inhibiting endosome fusion. These are used in research to block RAB5A function; no natural dominant-negative mutations are reported in ClinVar.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GDP binding |
| • GTPase activity | • protein domain specific binding |
| • early endosome membrane | • cytoplasm |
| • endosome | • plasma membrane |
| • regulation of endocytosis | • endosome fusion |
| • intracellular protein transport | • signal transduction |
Pathways
• Endocytosis
• Endosomal recycling
• EGFR signaling
• Autophagy
• Phagosome maturation
• VEGF signaling
Protein Summary
RAB5A is a 215-amino acid protein (UniProt P20339) with a molecular weight of ~23.6 kDa. It contains a conserved GTPase domain and a C-terminal hypervariable region that undergoes prenylation for membrane attachment. RAB5A localizes to early endosomes and plasma membrane clathrin-coated pits. It interacts with effectors such as EEA1, Rabaptin-5, and APPL1 to mediate vesicle tethering and fusion. Post-translational modifications include geranylgeranylation at C-terminal cysteines. RAB5A is essential for cell survival and proliferation, and its activity is tightly regulated by GEFs (e.g., Rabex-5) and GAPs (e.g., RN-tre).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB5A Knockout HEK293 Cell Line | EDJ-KQ1282 | Human | 5868 | Details Get a Quote |
| RAB5A Knockout A-549 Cell Line | EDJ-KQ20679 | Human | 5868 | Details Get a Quote |
| RAB5A Knockout HCT 116 Cell Line | EDJ-KQ20680 | Human | 5868 | Details Get a Quote |
| RAB5A Knockout HeLa Cell Line | EDJ-KQ20681 | Human | 5868 | Details Get a Quote |
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